Over the past year you may have seen preliminary
reports ofresults from the Multimodal Treatment
Study of Children withADHD (MTA). This is the
largest and most comprehensivetreatment
study of ADHD that has ever been conducted. Lastmonth, the initial papers reporting the results from this
studywere published. This is a landmark
study with a number ofimportant implications.

The December 1999 issue of the Archives of General Psychiatryincludes 2 papers that are based on this study.
The firstpaper titled "a 14 month randomized
clinical trial of treatmentstrategies for ADHD"
presents the major findings from thestudy.
The second paper, titled "Moderators and mediatorsof treatment response for children with ADHD" presents morefine-grained analyses in which factors that might
have influencedresponse to the different treatments
evaluated in the studywere examined.
In this summary, I will try to combine thefindings
that are reported in these two papers.

THE MTA STUDY

It is important to begin by providing an overview
of how thestudy was conducted and the questions
that it was specificallydesigned to address.
The study represented the combinedefforts of investigators at 6 different sites
around the countryand included 579 children
ages 7 to 9.9 years who werediagnosed as having
ADHD, Combined Type using state-of-the-art diagnostic procedures. (Children
diagnosed withthe hyperactive/impulsive subtype
or inattentive subtypewere excluded.
This decision was made because thecombined
type is the most frequently diagnosed type ofADHD). Approximately 20% of the participants
weregirls and about the same percentage was
African American.

After participants had been identified they
were randomlyassigned to 1 of 4 different treatment
conditions. Fourteenmonths later, the
participants were carefully evaluatedso that the impact of the different treatments
could beevaluated. Each treatment condition
is described below.

MEDICATION MANAGEMENT - Children in themedication
management condition received medicationtreatment
only. This began with a 28-day, double-blindplacebo-controlled trial in which the effects of 4 differentdoses of methylphenidate (the generic form of
Ritalin)were evaluated. The doses tested were 5,
10, 15, and20 mg. Children received a
full dose at breakfast andlunch, and then a
half-dose in the afternoon. Parent andteacher ratings of children's behavior on each dose werecompared by a team of experienced clinicians,
and thebest dose for each child was selected
by consensus.(In a double-blind placebo-controlled
trial, the childis receiving real medication
during some days and aplacebo during
other days. Neither the child, the teacher,nor the parent know when real medication is beingreceived and when placebo is being received.
Becauseof this, parent and teacher ratings
of the child's behaviorare not biased by the
knowledge that the child is onmedication.)

For children not obtaining an adequate response
tomethylphenidate during this initial trial,
alternatemedications were tested using non-double-blindprocedures in the following order until a satisfactorymedication and dose for the child was found:dextroamphetamine (the generic version ofdexedrine), pemoline (the generic version of
Cylert),and imipramine (a tricyclic antidepressant).

Note: This study was begun before Adderall
wasavailable for use which is probably why
it was notone of the medication options.

Of 289 participants initially assigned to
receivemedication in either the medication
managementcondition or the combined condition
(see below),256 (88.6%) successfully completed
this initial titrationperiod used to select
an effective medication. (For theremaining children, parents either refused to
try theirchild on medication, there were intolerable
side effects,or parents could not cooperate
with the careful titrationprocedures.)

For about 69% of the children completing the
initialmedication trial, an adequate response
was obtained withat least one of the doses
of methylphenidate, and they begantheir treatment
on this dose. Twenty-six children who didnot respond to methylphenidate were found to do well ondextroamphetamine and began on this medication.
A final32 did not begin on any medication because
they hadsuch a strong placebo response
that no clear benefits ofmedication could be
demonstrated.

In addition to this VERY CAREFUL initial trial
to determinethe optimal medication and dose
for each child, half-hourmonthly visits were
scheduled during which the providerfor that
child would review information about the child'sbehavior over the past month that was provided by parentsand teachers. After carefully reviewing
this information,dosage adjustments were made
using predetermined guidelines.Adjustments
that involved increases or decreases of morethan 10 mg/dose needed to be approved by a cross-sitepanel of experts.

By the end of the study - 14 months later
- about 74% ofparticipants of the 289 in the
medication or combined treatmentgroups were
being successfully maintained on ethylphenidate,10% on dextroamphetamine, and just over 1% on pemoline.Only two children were on any other type of medication.
(Asnoted above, some children who were assigned
to one ofthe medication groups never
received medication either becausetheir parents
refused or could not follow the initial trialprocedures.) Side effects had also been monitored monthlyand over 85% of the sample were reported to show
eitherno or mild side effects.

It is important to emphasize how different
this approach to medication management was from what often occurs in community
treatment. The primary differences are 1) the use of a double-blind
trial to establish the best initial dose and medication for each child; and,
2) regular follow-up visits to evaluate ongoing medication effectiveness
based on parent and teacher reports with systematic adjustments made as needed.

It is also important to note that almost
all children were judged to be effectively managed on one of the standard
stimulants (either methylphenidate or dextroamphetamine) and none were judged
to require a combination of medications to effectively manage their ADHD
symptoms. I think this underscores how rarely medications need to be combined
to treat ADHD when a careful procedure is
used to test out the different types of stimulants that are available.
This is discussed in another article in this issue of ADHD RESEARCH UPDATE
that you will find below.

The child-focused treatment was a summer treatmentprogram that children attended for 8 weeks, 5
days aweek, during the summer. This program
employedintensive behavioral interventions
that were administeredby counselors/aides who
were supervised by thetherapists conducting
the parent training. The basicmodel was
one in which children were able to earnvarious
rewards based on their ability to follow well-defined rules and meet certain behavioral expectations.Social skills training and specialized academicinstruction was also provided.

The school-based treatment had 2 components:
10 to16 sessions of biweekly teacher consultation
focusedon classroom behavior management strategies,
and12 weeks of a part-time paraprofessional
aide whoworked directly in the classroom with
the child.Throughout the school year, a Daily Report Cardwas used to link the child's behavior at school
toconsequences at home. The Daily Report
Card wasa 1-page teacher-completed ratings
of the the child'ssuccess on specific behaviors.
This was broughthome daily by the child
to be reviewed by parentswith rewards for a
successful day provided asindicated.

Consistent with what occurs in actual clinical
practice,the family and child's involvement
in behavioraltreatment was gradually tapered
over the 14 monthperiod. In most cases,
contact had been reduced to oncemonthly or
stopped altogether by the end of thisperiod.

The main
point to take away from this brief summary of the behavioral treatment that
children received is that it reflects absolute state-of-the-art practice
that would be virtually impossible to obtain in a typical community setting.
Thus, if anything, one would expect that the benefits of behavioral treatment
as implemented in this study would be likely to be greater than what would
typically be obtained.

COMBINED TREATMENT - Children in the combinedtreatment group received all of the treatments that areoutlined above. Individuals supervising
the child'sbehavioral and medical treatments
conferred regularly,and this was used to guide
overall treatment decisions.Consistent with
what has been found in prior studies,by
the end of the study, children in the combined groupwere being maintained on lower daily doses ofmethylphenidate than children who received medicationalone (Average doses were 31.2 mg/day for the
combinedgroup and 37.7 mg/day for the medication
only group).

COMMUNITY CARE - It clearly would not be ethicalto assign children with ADHD to a no-treatment controlgroup for a study that persisted for 14 months.
Instead,some children were randomly assigned
to a group thatreceived "community care".
Following their child'sdiagnosis of ADHD, parents
of these children were providedwith a list
of community mental health resources andmade
whatever treatment arrangements they preferred.

Most of the 97 children in this group (over
2/3s) receivedmedication from their own provider
during the 14 months.Several things are interesting
about the medication thesechildren received
compared to children who receivedmedication
as part of the study. First, community care childrenreceived less medication each day. For those treatedwith methylphenidate, the average daily dose
was 22.6 mg/daycompared to the average daily
doses of 31.2 mg and37.7 mg noted above.
In addition, community care childrenreceived
an average of 2.3 doses per day compared tothe 3 times/day dosing for children in the study.

Finally, while none of the children receiving
medication inthe study were maintained on either
clonidine or acombination of medications, 4
children seen by communityphysicians were treated
with clonidine and 10 childrenreceived
more than one medication. Thus, it appearsthat physicians in these communities were in some waysmore conservative in their use of medication
(i.e. prescribedlower doses of methylphenidate)
and in some way lessconservative (i.e.
were more likely to use medicationsother than
the widely used stimulants).

STUDY QUESTIONS

The MTA Study was designed to address 3 fundamentalquestions about the treatment of ADHD.
These questions areas follows:

1. How do long-term medication and behavioral
treatmentscompare with one another?

2. Are there additional benefits when they
are used together?

3. What is the effectiveness of systematic,
carefully deliveredtreatments vs. routine community
care?

THE RESULTS

There is a tremendous amount of data presented
in thesepapers and it is really not possible
to summarize it all.Below, however, are what
I found to be the most importantfindings.

First, let me list the variety of different
outcomes thatwere assessed and reported.
These include:

* Academic achievement - assessed by standardized tests;(It is unfortunate, I think, that more frequent measures
ofacademic performance in the classroom were
notcollected. These tend to be more sensitive
to change thanscores on standardized achievement
tests. Thus, thereliance on achievement
tests alone as the measure ofacademic performance
may not have enabled importantchanges in academic
functioning to be captured).

In considering the results presented below
itis important to place them in this overall
context:

Children in all 4 groups (i.e. medication
only, behavioraltreatment only, combined
treatment, and treatment in thecommunity as
chosen by parents) showed significantreductions
in their level of symptoms over time inmost
areas. Thus, even though some treatments wereclearly superior to others in certain domains, overall,even children receiving the "least effective"
treatmenttended to show important improvement.
Thus, thesedata should not be interpreted in
a framework of "whatworked" and "what did not
work". Instead, it is amatter of what
seemed to be most effective among treatmentsthat all showed some positive effects.

1. How do
long-term medication and behavioral treatmentscompare with one another?

On all the other outcome measures reported,
medicationmanagement and behavioral treatment
did not differsignificantly.

Thus, although medication was found to be
superior tobehavioral treatment on core ADHD
symptoms, thisdid not extend to other important
areas of children'sfunctioning such as oppositional
behavior, peerrelations, and academic achievement.

Combined treatment and medication management
treatmentdid not differ significantly in any
of the 6 domains. This suggests that for most children with ADHD,
adding behavioral intervention on top of well-conducted medication management
is not likely to yield substantial incremental gains.

As can often be true with statistical analyses,
however,this conclusion changes somewhat depending
on how youlook at the data.For example, when you look at the rank ordering on differentoutcomes for children in the different groups,
children in thecombined treatment group did
best on 12 of 19 outcome measureswhile those
in the medication management group were best ononly 4. In addition, when the individual outcome measuresare combined into composite measures, or when
children'soutcomes are grouped into excellent
response vs. less dramaticresponse categories,
children receiving combined treatmentdid modestly,
but significantly, better.

Compared to behavioral treatment alone, combined
treatmentwas found to be superior on parent
and teacher ratings ofprimary ADHD symptoms,
on parent ratings of aggressive/oppositional
behavior, on parent ratings of children'sinternalizing symptoms, and on results of the standardizedreading assessment. Thus, adding medication
to thetreatment of a child already receiving
behavioral interventionis likely to yield substantial
benefits for most children.

3. Did participants
assigned to each of the 3 MTA treatments(i.e. medication management, behavioral treatment, andcombined treatment) show greater improvement
than childrenreceiving community
care?

The answer to this question was clear and
straight forward.Both combined treatment and
medication treatment weresuperior to community
care for parent and teacher reports ofprimary
ADHD symptoms while behavioral treatmentwas not.In general, parents
and teachers tended to report a decline ofapproximately
50% in inattentive and hyperactive/impulsivesymptoms for children in the medication and combined treatmentgroups. For children receiving community
care, the declinesreported were in the 25% range
and were comparable to thosereported for children
receiving behavioral treatment.In the non-ADHD
domains, (e.g. oppositional behavior,internalizing
symptoms, social skills, and reading achievement)combined treatment was always superior to community treatment,with particularly dramatic differences in parent
reports of oppositional/aggressive behavior.
Medication management and behavioral treatmentwere superior to community treatment on a single domain
only.

Overall, these data indicate that although
children treated inthe community made modest
gains over the course of thestudy, those receiving
medication treatment in the MTAstudy - either
alone or in combination with behavioraltreatment
- did significantly better. This was especiallytrue for children receiving the combined treatments.Possible reasons for this will be discussed in the
summarysection below.

FOLLOW UP ANALYSES

In addition to the analyses reported above,
the MTA researchgroup was interested in whether
the effect of the differenttreatments may have
differed depending on certaincharacteristics
of the children. Thus, they also looked atwhether similar results were obtained:

1. for boys vs. girls - as noted above
girls made up about20% of the
overall sample;

2. for children with and without an
additional diagnosis ofeither
Oppositional Defiant Disorder (ODD) or ConductDisorder (CD);

3. for children with and without a co-occurring
anxiety disorder;

In general, there were no substantial differences
in the effectivenessof the different treatments
depending on these variables. Thus,similar treatment results were found for boys
and girls and forchildren with and without
a co-occurring behavior disorder. Therewas some indication, however, that for children
with a co-occurringanxiety disorder, behavioral
intervention alone was as effectiveas both medication management and the combined
treatment. Itis also worth noting, however,
that children with anxiety disorderswho received medication only did not have a poorer
response tomedication than other children.
Thus, prior and less intensivestudies in which it has been reported that children
with ADHD andan anxiety disorder do not do
as well on stimulant medication arecontradicted by these results.

THE IMPACT OF TREATMENT
ADHERENCE

In a final set of follow up analyses, the
researchers also analyzedthe results according
to how children and parents were able toadhere to the prescribed treatments. Thus,
children assigned tothe medication management
condition were divided into 2 groupsdepending on whether they or not medication treatment
wasimplemented as recommended and whether the
family attended atleast 80% of the scheduled follow-up visits where
the ongoingimpact of the medication could be
monitored.For behavioral treatment, children
were divided into 2 groupsdepending on whether
or not parents attended at least 75% ofthe
scheduled parent group meetings, the child attended at least75% of the summer treatment program, and whether the child
andparaprofessional working with the child
in the classroom wereboth present for 75% of
the intended days. If any one of these3 conditions were not met, the behavioral treatment was
notconsidered to have been implemented as intended.For the combined treatment group, families had
to adhere to theguidelines for both medication
management and behavioraltreatment to be placed
in the "as intended" group. Otherwise,they were placed in a group that was judged to not haveadhered to treatment as recommended.

HOW WELL WERE TREATMENT
RECOMMENDATIONSFOLLOWED?

The first thing that is interesting to note
is the percentage offamilies in the 3 MTA study
treatment conditions that wereable/willing to
adhere to treatment as recommended.Acceptance/attendance
was higher for the medication managementtreatment
(78% of families completing treatment as intended)than in behavioral treatment (63%) or combined treatment
(61%).Thus, even when state of the art behavioral
treatment wasprovided to families at NO CHARGE,
almost 40% of familieswere unable and/or unwilling
to fully take advantage of it.

In terms of the impact of treatment adherence
on child outcome,significant effects were found
only for the medication managementgroup. Thus, for children where the recommended
medicationmanagement procedure was followed
more closely, the outcomeswere significantly better. For the behavioral
and combinedtreatment conditions, in contrast,
no differences in child outcomesdepending on treatment adherence were found.
It seems reasonablethat the absence of an effect
of adherence for the combined treatmentgroup
is that most of the families in the non-adherent categorywere there because they failed to comply with the behavioraltreatment procedure, and that these children
did as well as the"adherers" because of the
benefits they derived from the medication.

SUMMARY AND IMPLICATIONS

There is a LOT here to digest. Before
trying to pull together whatseem to me to be
some of the fundamentally important implicationsof this study, it is important to note that many additional
paperswill be emerging from this work.
In particular, although the childrenin this
study are no longer receiving their treatment as part of the study,they do continue to be followed. This will
enable the researchers toexamine the sustained
impact of different treatments beyond the 14month outcome data that were presented in this initial paper.
Thus, itis certainly possible that results
based on 2 or 3 year outcomes maylook somewhat
different from what was found after 14 months.

Several other caveats are important to note.
First, in this study childrenwith the inattentive
subtype of ADHD were specifically excluded.Thus,
these results can not be generalized to children with this subtypeof ADHD.

Second, treatments investigated in this study
were limited to those withthe greatest empirical
support to date: medication and behavioraltreatment.
This study thus sheds no light on the effectiveness of othertypes of treatment for ADHD such as dietary interventions,
biofeedback,etc. Additional research
on other treatment options that is as carefuland well conducted as this study is certainly needed.

That being said, what are some of the important
conclusions to be drawnfrom the data presented
so far and what do these results mean for parentsand health care providers who are concerned about doing
the best theycan for their child and their
patients? (Please note that these are myopinions, and that other scientists, health care providers,
and educatorsmight reach somewhat different
conclusions from those I present. Also,it is important to stress that conclusions about treatment
are predicatedon a careful evaluation of ADHD
having been done in the first place, aswas the case in this study).

For many children with ADHD, Combined
Type, medication alone islikely
to be an effective and perhaps even sufficient treatment whencare is taken to determine the optimal
medication/dose for each childand when the ongoing effectiveness of medication is carefully
monitored.

I am aware that many people may find this
conclusion to bedistasteful, but I think it
is a reasonable one to draw fromthese data.
Remember, I am a Ph.D. not an M.D., and thus donot provide medication myself.

Although there was some indication for a mild
to modest superiorityfor combined treatment
on some outcomes, overall, children whoreceived
medication alone tended to do about as well as children whoreceived the combined treatment. This was true even
though the behavioraltreatment provided in
this study was far more intensive than would beroutinely available in any community setting. In fact,
I think it is reasonableto say that the behavioral
treatment provided in the MTA setting couldsimply
not be duplicated in any other context.

This does not mean that there is no place
for behavioral treatment inthe management of
children with ADHD (see below). To me, however,it suggests that a reasonable approach may be to begin with
carefullyconducted medication trial to be certain
that the maximum possible benefitsfrom
medication are being attained.

When this has been done, and there are
still important difficulties in a child's behavioral, academic, and/or social
functioning, adding behavioral or other psychosocial interventions that specifically
target these residual problems should be pursued. These interventions can
make an IMPORTANT difference for an individual child, even though the benefits
at a group level are apparently not so dramatic.

It should also be noted that combining behavioral
treatment withmedication management did enable
children to be maintained on asomewhat lower dose of medication. The
authors note, however,that the actual significance
of this difference is unclear. Many parents andphysicians may regard this as quite important,
however.

Thus, ifmaintaining your child on the minimum dose of medication required
to yield optimum results is important to you, than combining medication treatment
with carefully executed behavioral interventions is likely to be required.

Intensive and well-conducted behavioral
treatment can also be aneffective
option for treating children with ADHD. For mostchildren it will probably be less effective
than careful medicationtreatment,
however, and it may be hard for parents to implementas directed.

Once again, I think it is very important to
note that the behavioralinterventions implemented
in this study were also associated withsignificant reductions in ADHD symptoms and some
improvementin other domains. The reductions
in ADHD symptoms were notas great as for the medication management group,
but in other areas,no statistically significant
differences between these treatments werefound.

There are, however, some important points
to keep in mind here. First,as noted
above, the intensity and quality of the behavioral treatmentprovided to children in this study could probably
not be matched inany other context - it is
just not available outside of a research setting.Whether a less intensive behavioral treatment would also
be shownto produce significant gains over a
14-month period is thus unknown.Chances are,
however, that behavioral treatment as typically practicedwould probably not be as helpful as what was able to be
provided inthe study.

Second, it is very difficult for parents to
persist with the type ofbehavioral treatment
used in this study - about 40% were not ableto adhere to the treatment even though it was
offered in the studyat no charge.

Finally, it should be noted that although
not many statisticallysignificant differences
between behavioral treatment and medicationmanagement were found, 26% of the parents whose
child wasreceiving behavioral treatment only
as part of the study opted toadd medication
to their child's treatment. In contrast, only 2%of parents whose child was receiving medication opted to
addbehavioral treatment. This certainly
suggests that many parents ofchildren receiving
behavioral treatment only were less likely to besatisfied with the results of their child's treatment.

Overall, I think a reasonable conclusion is
that behavioralintervention - when used in
isolation - is likely to be less effectivethan
medication management, harder for parents to implement, andmore expensive. To me, this suggests that themost appropriate use of behavioral treatment
for many childrenmay be not as the sole intervention,
but as something that iscarefully incorporated
into a child's treatment to addressproblems
that are not sufficiently helped by medication alone.

How medication is prescribed makes a
difference and parents needto
insist that their child's physician have an objective procedure inplace to determine the optimum medication/dose
for their child, andto
carefully monitor the ongoing effectiveness of medication treatmentfor their child.

An inescapable conclusion from this study
is that children who receivedmedication from
the MTA staff did significantly better than children whoreceived medication from community physicians. Although
the reasons forthis can not be determined with
certainty, it seems quite likely that this wasbecause of the care that was taken initially to determine
the optimum dosefor each child, and to then
carefully monitor how the child was doing andto make adjustments as needed. Parents need to insist
that this be done fortheir child. Physicians
need to begin using more objective procedures forevaluating medication response on a routine basis.
This is not hard to dobut it does take
a bit of time. (Remember, you can easily use the ADHDMonitoring System that you received when you subscribed
to evaluatethe ongoing effectiveness of your
child's treatment).

There are some differences in medication treatment
in the MTA group andthe community care group
that we do know with certainty.

1. Children
treated by community physicians may be routinely under-medicated.

Children treated with medication alone in
the MTA study who didwell on methylphenidate
received an average of almost 38 mg/dayin 3 separate doses. Children treated with
methylphenidate in thecommunity received an
average of about 23 mg/day - a dose reductionof about 40% - spread over 2 doses per day.
Even though childrenreceiving medication as
part of the combined treatment were on lowerdoses then the medication only group, they still received
a substantiallyhigher dose than the community
treated participants.Because MTA-treated children
did much better, it seems reasonable toconclude
that many children treated in the community were not receivingenough medication to obtain the maximum possible benefit.

Please do not interpret these data to mean
that every child should beon the average dose
used in the MTA study. Remember, some childrendo better on lower doses and some on higher, and the best
dose for eachchild needs to be determined using
a careful trial.

Also, it is important to remember that the
daily total dose and 3 administrationper day
figure noted above was for methylphenidate and would certainlybe different for other medications. For example,
recent data suggeststhat Adderall - not used
in this study because it was not available whenthe study was conducted - can produce at least comparable
benefitsto methylphenidate with fewer administrations
per day.2.

Children treated by community physicians
are often put on non-stimulantmedications
and/or combinations of medications that are not necessary.

I think this is a really important point.

Recall that virtually every MTA participant
receiving medication wasable to be managed
effectively on either methyphenidate or the genericversion of dexedrine.

Very few needed to be prescribed a different
class of medication like anantidepressant
and not a single child was prescribed a combination of meds(e.g. methylphenidate and clonidine). In contrast,
over 10% of childrentreated by community physicians
were on multiple medications and over16% were
treated with an antidepressant.

What I conclude from these data is that
when stimulant medicationis prescribed
carefully, there will be VERY few cases where anotherclass of medication needs to be used and ALMOST NO CASES
wheremultiple medications are
needed.

I think that what may often happen in the
community is that physiciansgive up on stimulants
before an adequate dose has been tried, or beforealternative stimulants have been tried. Instead, a
switch is made toa different type of drug or
a new drug is combined with the stimulants.

This is problematic for several reasons.
First, no other class of drugshas been shown
to be as effective as stimulants for treating ADHD.Second, despite the concerns that many people have about
possibleadverse health consequences of stimulant
medications, availablesupport for the long-term
safety of these medications is greater thanfor
the other medications that are often switched to or added.

So, if I were a parent of a child with ADHD,
I would ask LOTS ofquestions of my child's
physician before I switched him or her toa non-stimulant medication or had my child take
multiple medication.(e.g. "Why don't we try
a higher dose first?" Why don't we testthe effect of another type of stimulant first?")

If you are a provider of medication, I think
these data should becarefully considered before
such a switch is recommended.

This summary has been quite long and I hope
it has been clearenough to give you a good
feel for the results and significanceof this
important study. As noted earlier, there will be manymore papers that emerge from this project, and I will be
sureto include them in ATTENTION RESEARCH UPDATE
as theyare published.

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